(S)-2-Methylproline

(S)-2-Methylproline is a privileged building block in peptidomimetic drug design, most notably as the P2 core residue in multiple approved HCV NS3/4A protease inhibitors including glecaprevir and voxilaprevir. The α‑methyl group of (S)-2-Methylproline creates a quaternary center that locks the N–Cα bond in a rigid conformation, dramatically enhancing the metabolic stability of peptide bonds on its N‑terminal side. Process chemistry groups value (S)-2-Methylproline because it can be readily incorporated into growing peptide chains using standard coupling reagents without epimerization. Cosperpharm ensures that (S)-2-Methylproline is supplied with an enantiomeric excess exceeding 99.5%, eliminating the risk of diastereomeric contamination in the final macrocyclic drug substance.

Product Parameters

Why Cosperpharm?

Cosperpharm manufactures (S)-2-Methylproline via a scalable, enantioselective route that avoids the use of hazardous methylating agents and reliably achieves optical purity exceeding 99.5% e.e. Our process begins from L‑proline and preserves the stereochemical integrity through a controlled enolate alkylation. Each batch is released after confirmatory testing by chiral HPLC, achiral HPLC, specific rotation, and water content. We can supply this amino acid in quantities ranging from 25‑g laboratory packs to 50‑kg commercial drums, all accompanied by a full Certificate of Analysis and, when required, a technical dossier supporting ANDA or NDA submissions for antiviral drug products.

Product Advantages

1. Protease‑Stable Quaternary Center – The α‑methyl group blocks enzymatic cleavage of the N‑terminal peptide bond, critical for oral bioavailability of macrocyclic peptides.

2. Natural Proline Configuration – The (S)‑stereochemistry matches the naturally occurring amino acid, preserving biological recognition.

3. Crystalline Solid – Non‑hygroscopic, free‑flowing powder that can be weighed accurately without special precautions.

4. Ready for Peptide Coupling – Compatible with standard Fmoc‑SPPS or solution‑phase protocols; no protecting group manipulation required.

5. GMP‑Ready Supply – Cosperpharm can deliver this material under full cGMP compliance, with full traceability and stability data.

Application Scenarios

1. HCV Protease Inhibitor Core

Serves as the P2 fragment in glecaprevir, voxilaprevir, and investigational macrocyclic antivirals.

2. Macrocyclic Peptide Stabilization

Introduces a rigid turn element in cyclic peptides targeting protein‑protein interactions.

3. β‑Hairpin Mimic Design

Used to nucleate β‑sheet structures in antimicrobial peptides and antibody mimetics.

4. Chemical Biology Tools

Incorporated into fluorogenic substrates and activity‑based probes for profiling prolyl peptidases.

5. Process Development

Consistent solid form facilitates accurate charging in kilogram‑scale solution‑phase peptide syntheses.

Contact Us

To introduce conformational rigidity into your next peptide therapeutic, contact Cosperpharm’s amino acid product group — we can ship a characterization sample immediately and provide a quote for pilot‑scale quantities within your timeline.